Tetrachloro-p-benzoquinone induces hepatic oxidative damage and inflammatory response, but not apoptosis in mouse: the prevention of curcumin.

Abstract

This study investigated the protective effects of curcumin on tetrachloro-p-benzoquinone (TCBQ)-induced hepatotoxicity in mice. TCBQ-treatment causes significant liver injury (the elevation of serum AST and ALT activities, histopathological changes in liver section including centrilobular necrosis and inflammatory cells), oxidative stress (the elevation of TBAR level and the inhibition of SOD and catalase activities) and inflammation (up-regulation of iNOS, COX-2, IL-1β, IL-6, TNF-α and NF-κB). However, these changes were alleviated upon pretreatment with curcumin. Interestingly, TCBQ has no effect on caspase family genes or B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) protein expressions, which implied that TCBQ-induced hepatotoxicity is independent of apoptosis. Moreover, curcumin was shown to induce phase II detoxifying/antioxidant enzymes HO-1 and NQO1 through the activation of nuclear factor erythroid-derived 2-like 2 (Nrf2). In summary, the protective mechanisms of curcumin against TCBQ-induced hepatoxicity may be related to the attenuation of oxidative stress, along with the inhibition of inflammatory response via the activation of Nrf2 signaling.

• Authors: Demei Xu, Lihua Hu, Chuanyang Su, Xiaomin Xia, Pu Zhang, Juanli Fu, Wenchao Wang, Duo Xu, Hong Du, Qiuling Hu, Erqun Song, Yang Song
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 280 Issue 2 Pg. 305-13 (Oct 15 2014) ISSN: 1096-0333 [Electronic] United States
• PMID: 25123790 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Benzoquinones
• Hydrocarbons, Chlorinated
• Interleukin-6
• NF-E2-Related Factor 2
• NF-kappa B
• Nfe2l2 protein, mouse
• Proto-Oncogene Proteins c-bcl-2
• tetrachlorobenzoquinone
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Aspartate Aminotransferases
• Alanine Transaminase
• Caspases
• Curcumin

Topics

• Alanine Transaminase (blood)
• Animals
• Apoptosis (drug effects)
• Aspartate Aminotransferases (blood)
• Benzoquinones (toxicity)
• Caspases (metabolism)
• Curcumin (toxicity)
• Hydrocarbons, Chlorinated (toxicity)
• Inflammation (chemically induced)
• Interleukin-6 (analysis)
• Liver (drug effects, metabolism, pathology)
• Male
• Mice
• NF-E2-Related Factor 2 (physiology)
• NF-kappa B (analysis)
• Nitric Oxide Synthase Type II (metabolism)
• Oxidative Stress (drug effects)
• Proto-Oncogene Proteins c-bcl-2 (analysis)